tbuckley/cabot-search huggingface dataset:
Abstract 23: Genome Wide Association Study and Multi-Ancestry Meta-Analysis Identify Common Variants Associated With Carotid Artery Intima Media Thickness
Authors: Abbas Dehghan, Jian Huang, Natalie Hesbani, Palwende Romuald, Marjan Zare, Nora Franceschini, Paul de Vries, Ioanna Tzoulaki, Devendra Meena
Journal: Circulation (2023)

Carotid artery intima-media thickness (cIMT) is a measurement of subclinical atherosclerosis that predicts future cardiovascular events, including stroke and myocardial infarction. Genome-wide association studies (GWAS) in the past have identified only a fraction of the genetic variants associated with cIMT. We performed the largest GWAS to date for cIMT in a multi-ancestry meta-analysis in up to 131,000 individuals of African, Asian (Chinese), Brazilian, European, and Hispanic ancestries. Our study identified 57 independent loci (51 loci from the multi-ancestry single variant analysis of which 17 are novel, P&lt;5x10 -8 ; 6 novel in gene-based analysis from single variant analysis, P = 2.6x10 -6 ) associated with cIMT. Gene-based, tissue-expression and gene-set enrichment analyses revealed novel genes of potential interest and highlighted significant relationships between vascular tissues (aorta, coronary and tibial arteries) and genetic associations. We found strong genome-wide correlation between cIMT and various cardiometabolic, smoking and lipid traits. Using Mendelian randomisation, our analyses provide robust evidence for causal associations between cIMT and several clinically relevant traits, including lipids, blood pressure, and waist circumference. Our results provide the first evidence of substantial pleiotropy in colocalisation signals between APOE SNPs and metabolite biomarkers for coronary artery disease and cIMT but not for Alzheimer's disease.In summary, we identify 57 loci robustly associated with cIMT that are expressed in a range of vascular tissue types including aorta, coronary and tibial arteries. Our findings suggest a bidirectional relationship between cIMT and hypertension but do not support a link between atherosclerosis and Alzheimer’s disease based on the APOE locus.
Abstract P266: Complex Patterns of Early Life Adversity Vary by Gender: Associations With Cardiometabolic Health and Pre-Heart Failure Among Hispanics/Latinos in the Midlife
Authors: Ayana K April-Sanders, Linda Gallo, Un Jung Lee, Barry E Hurwitz, Martha L Daviglus, Gregory A Talavera, Bonnie Shook-Sa, Carmen R Isasi, Carlos J Rodriguez
Journal: Circulation (2023)

Background: Early life adversities (ELA) are known risk factors for cardiovascular disease, but less understood is how distinct configurations of ELA impart differential risks for cardiometabolic health and heart failure (HF) in adulthood. Objective: To determine distinct profiles of ELA and assess whether there are associations between the resultant profiles and multiple indicators of cardiometabolic disease and pre-HF among Hispanic/Latino adults. Methods: Data from the Hispanic Community Health Study/Study of Latinos SCAS and ECHO-SOL (N=1143, mean age 55.9±0.4 years, 58.2% female) were used. Latent class analysis was used to identify the optimal number of classes characterizing ELA co-occurrence overall and by gender. Prevalent pre-HF was defined as systolic dysfunction (left ventricular (LF) ejection fraction &lt;50%/ global longitudinal strain &gt;15%) or diastolic dysfunction (≥ Grade 1) or LV remodeling (LV mass index &gt;115 for males, &gt;95 for females/ relative wall thickness &gt;0.42). Weighted multivariable logit models were used to examine associations. Results: The best fitting latent classes and characterization are shown in Figure 1. By gender, ELA profiles were associated with cardiometabolic factors. E.g., females with high adversity had greater odds of obesity than those with a low adversity (OR=2.27, 95% CI: 1.39 - 3.72). Alternatively, males experiencing household dysfunction had lower odds of high cholesterol than those with low adversity (OR=0.39, 95% CI: 0.19 - 0.80). Associations were not explained by age, childhood economic hardship, nativity, and Hispanic/Latino background. ELA profiles were not associated with pre-HF (e.g., high adversity OR=0.60, household dysfunction OR=0.75; all p&gt;0.05). Conclusions: Distinct patterns of ELA among Hispanic/Latino adults vary by gender; females experience more complex and varied patterns of adversity. Exposure to specific patterns of ELA were associated with several cardiometabolic outcomes, but no associations were found with any measures of pre-HF.
Abstract MP22: Plasma Metabolomic Profiles Associated With Mortality and Longevity in a Prospective Study of 13,401 Individuals
Authors: Fenglei Wang, Anne-Julie Tessier, Liming Liang, Clemens Wittenbecher, Danielle Haslam, A H Eliassen, Kathryn M Rexrode, Deirdre K Tobias, Jun Li, Oana Zeleznik, Meir J Stampfer, Francine Grodstein, Miguel Martínez-González, Jordi Salas-Salvado, Clary Clish, Kyu Ha Lee, Qi Sun, Frank Hu, Marta Guasch-Ferré
Journal: Circulation (2023)

Background: Recent advances in metabolomic studies have shown promise in elucidating the biological pathways underpinning aging processes and mortality in animal models, but data in humans are lacking. We aimed to evaluate the associations between metabolite profiles, all-cause and cause-specific mortality, and longevity. Methods: Within three prospective cohorts (Nurses’ Health Study [NHS], NHSII, and Health Professional’s Follow-up Study), we measured plasma metabolites from 11,523 participants (mean age 54 years, 86% female) using high-throughput liquid chromatography-mass spectrometry. Participants were free of cardiovascular disease and cancer at blood collection. Metabolome-wide association analyses were conducted for all-cause, cardiovascular, and cancer mortality using Cox proportional hazards regression and longevity (attaining 85 years of age) using logistic regression. Both pre-defined and data-driven metabolite groups were also evaluated. We further developed a multi-metabolite profile score for all-cause mortality using an elastic-net regularized Cox model and assessed its associations with mortality and longevity. Results for all-cause mortality were replicated among 1878 participants (mean age 67 years, 58% female) from the PREDIMED trial. Results: We documented 4252 deaths (including 864 cardiovascular deaths and 1070 cancer deaths) and 3048 achieving longevity over a median follow-up of 22.6 years in the NHS/NHSII/HPFS, and 126 deaths during a follow-up of 4.7 years in the PREDIMED. Higher levels of three nucleosides (N2,N2-dimethylguanosine, pseudouridine, and N4-acetylcytidine), 4-acetamidobutanoic acid, triacylglycerols with ≤56 carbons and ≤3 double bonds, and several other lipids were associated with increased risk of all-cause mortality and corresponding decreased likelihood of longevity; whereas L-serine, L-glutamine, and TAGs with &gt;56 carbons or &gt;3 double bonds were associated with lower mortality risk and higher odds of achieving longevity. A multi-metabolite profile score comprising 73 metabolites was positively associated with all-cause (HR per 1-SD increment=1.25 [95% CI: 1.21, 1.30] in NHS/NHSII/HPFS and 1.47 [95% CI: 1.22, 1.78] in PREDIMED), cardiovascular (HR=1.34 [95% CI:1.24, 1.45]), and cancer mortality (HR=1.15 [95% CI:1.08, 1.24]) and inversely associated with longevity (OR=0.79 [95% CI: 0.74, 0.86]). Conclusions: We identified multiple metabolites associated with mortality and longevity. Our findings provide insights into the biological pathways that lead to death and open up new avenues to incorporate these metabolomic markers in clinical and research settings.
Abstract P573: Educational Assortative Mating and Cardiovascular Outcomes
Authors: Miremad Moafi-Madani, Muhammad Baig, Mary Roberts, Charles Eaton
Journal: Circulation (2023)

Objective: To estimate the association between educational assortative mating and cardiovascular outcomes among postmenopausal women in the Women’s Health Initiative study. Background: Between 1970 and 2015, the number of dual professional couples almost tripled. For instance, the likelihood of male attorneys marrying female lawyers and male doctors marrying female doctors has increased. Studies have proposed that educational assortative mating—people marry those with similar educational attainment--affects health disparities through increasing income inequality, creating differential levels of healthcare access, and based on the social cognitive theory, exchanging health knowledge and sharing healthy behaviors. Methods: We compared women living in three homogenous educational pairings; married women and spouses who both have 1) a high school degree or lower, 2) an associate or college degree, and 3) an MS, Ph.D., or professional degree. We used logistic regression models for prevalent outcomes (HTN, CHD, HF) at WHI baseline and Cox proportional hazard regression models for incident outcomes, all adjusted for age and total household income. To consider effect modification by membership in different racial or ethnic groups, we also conducted a stratified analysis. Results: We found significant associations between educational assortative mating and all cardiovascular outcomes within all groups of women. We found higher odds of prevalent cardiovascular outcomes ranging from 47 to 98 percent and a higher hazard of incident outcomes ranging from 24 to 56 percent. The strongest associations were found for prevalent and incident heart failure among Black women. Conclusion: This study provides evidence that educational assortative mating is likely a contributor to widening disparities in cardiovascular outcomes within and between racial groups of women.
Abstract 65: DNA Methylation at <i>ABCG1</i> and Long-Term Changes in Adiposity in Response to Diet Interventions: The POUNDS Lost Trial
Authors: Xiang Li, Xiaojian Shao, Qiaochu Xue, Minghao Kou, Elin Grundberg, George A Bray, Frank M Sacks, Lu Qi
Journal: Circulation (2023)

Introduction: Epigenome-wide association studies identified that DNA methylation (DNAm) at the ABCG1 gene (cg06500161) was associated with obesity. However, little is known about whether DNAm at ABCG1 is associated with long-term changes in adiposity and body fat distribution in response to dietary weight-loss interventions. Hypothesis: We hypothesized that participants with varying DNAm at ABCG1 might respond differently to dietary weight-loss interventions on long-term changes in adiposity and body fat distribution. Methods: The current study included 673 participants with overweight/obesity, who were randomly assigned to 1 of 4 diets varying in macronutrient components. Blood DNAm level was profiled by a high-resolution methylC-capture sequencing at baseline. The regional DNAm at ABCG1 was defined as the average methylation level over CpGs within ± 250 bp of cg06500161. Two-year changes in adiposity and Computed Tomography (CT)-measured body fat distribution were calculated. Results: We found that regional DNAm at ABCG1 significantly interacted with dietary protein intake on long-term changes in body weight and waist circumference (WC) at 6 months and 2 years (P-interaction&lt;0.05 for all, Figure ). Among participants assigned to an average-protein (15%) diet, lower regional DNAm at ABCG1 was associated with greater reductions in body weight and WC at 6 months and 2 years, while opposite associations were found among those assigned to a high-protein (25%) diet. Similar interactions were also observed for body fat distribution, including visceral adipose tissue, subcutaneous adipose tissue, deep subcutaneous adipose tissue, and total adipose tissue at 6 months and 2 years (P-interaction&lt;0.05 for all). Conclusion: Our data indicate that DNAm at ABCG1 interacted with dietary protein intake on long-term changes in adiposity and body fat distribution. Participants with hypomethylation at ABCG1 benefited more in long-term improvement in adiposity and body fat distribution by consuming an average-protein diet.
Abstract P188: Diabetes Prevalence and its Risk Factors Among Veterans by Sexual Orientation
Authors: Meredith S Duncan, Carl Streed, Lauren B Beach, John O'Leary, Melissa Skanderson, Joseph Goulet
Journal: Circulation (2023)

Introduction: There is evidence that lesbian, gay, and bisexual (LGB) adults have poorer cardiovascular health than their heterosexual peers, but studies of the association between sexual orientation (SO) and diabetes mellitus (DM) have been few. Prior studies have largely been cross-sectional, rely on self-reported data, and have small sample size; findings have been mixed. To further investigate this association, large nationwide cohorts with objective data capture are needed. Methods and Results: We used data from the Veterans Healthcare Administration Lesbian, Gay, Bisexual, Transgender EHR cohort which includes veterans with ≥2 encounters October 1, 2009-September 30, 2019. The first clinic visit in this window was the index date with the baseline date one year later; the subsequent year served as a baseline period for observation of prevalent disease and comorbidities. We did not include transgender veterans in this analysis in order to focus on SO rather than on the intersection of SO with gender identity. The SO of 1,108,990 veterans was identified using a natural language processing tool; 185,788 veterans were classified as LGB. Prevalent DM (ICD-9/10 codes or HbA1c≥6.5%) was present among 193,330 veterans (32,986 LGB). We first examined sample characteristics by sex and SO. Mean age (years) and BMI (kg/m 2 ) were similar across SO in women (age: 41, BMI: 29) and men (age: 53, BMI: 30). Although the distribution of race was similar across groups, LGB men and women were more likely to be of Hispanic ethnicity (11%, both sexes) than non-LGB men and women (6% and 8%, respectively). Current smoking was more prevalent among LGB (44% men, 39% women) than among non-LGB veterans (40% men, 30% women). We used logistic regression to assess the association between SO and DM. Adjusting for age, sex, race, Hispanic ethnicity, BMI, smoking status, health insurance, marital status, and enrollment priority group (based on military service history, disability and income), LGB veterans had 1.12 [1.10, 1.13] times the odds of DM versus non-LGB veterans. Among women, those classified as bisexual (0.87 [0.74, 1.01]) or lesbian (1.03 [0.97, 1.10]) did not have significantly different odds of DM than non-LGB women. Among men, bisexual men had lower odds of DM (0.86 [0.80, 0.93]) while gay men had higher odds (1.04 [1.01, 1.06]) than non-LGB men. In both men and women, sexual minority individuals whose SO could not be classified had greater odds of DM than their non-LGB peers (women: 1.15 [1.08, 1.23]; men: 1.25 [1.22, 1.28]). Conclusion: This is one of the first studies to examine DM in a veteran population stratified by SO. Our sex-specific findings highlight the importance of examining each SO group separately, in addition to jointly, as to further elucidate the association between SO, cardiovascular risk factors, and general cardiovascular health. Future work will examine the intersection of SO with gender identity.
Abstract 43: Genetic, Sociodemographic, Lifestyle, and Clinical Risk Factors of Coronary Artery Disease Recurrent Events: Population-Based Cohort Study
Authors: So Mi J Cho, Satoshi Koyama, Michael C Honigberg, Ida Surakka, Aniruddh P Patel, Romit Bhattacharya, Hokyou Lee, Hyeon Chang Kim, Pradeep Natarajan
Journal: Circulation (2023)

Introduction: Contemporary guidelines remain to uniformly classify patients with established atherosclerotic cardiovascular disease as high risk despite substantial heterogeneities in risk factors distributions. We examined the independent associations and relative predictabilities of genetic, sociodemographic, lifestyle, and clinical risk factors on coronary artery disease (CAD) recurrence. Methods: From population-based UK Biobank cohort, we identified 7,024 participants aged 40-69 years with established CAD at enrollment. Based on multivariable Cox regression model, we evaluated the hazard ratio (HR) and discrimination index of age at enrollment, age at first CAD diagnosis, sex, smoking, physical activity, diet, sleep, socioeconomic deprivation, body mass index, blood pressure, lipids, glucose, lipoprotein(a), C-reactive protein, estimated glomerular filtration rate, statin prescription, and CAD polygenic risk score (PRS) on first CAD recurrence since enrollment. Results: Over a median [IQR] follow-up of 11.6 [4.0] years, 2,003 (28.5%) recurrent CAD events occurred. Of studied risk factors, the HR [95% CI] for CAD recurrence was the most pronounced with current smoking (1.35 [1.13-1.61]) and per SD increase in age at first CAD (0.74 [0.67-0.82]). Moreover, age at enrollment, Townsend Deprivation Index, sleep quality, cholesterols, glucose, renal function, C-reactive protein, and CAD PRS also significantly associated with recurrence. CAD PRS (C index: 0.58 [0.57-0.59]) largely predicted CAD recurrence, followed by high-density lipoprotein (HDL) cholesterol (0.57 [0.57-0.58]) and age at first CAD (0.57 [0.56-0.57]). In addition to traditional risk factors, a comprehensive model improved the C index from 0.64 [0.63-0.65] to 0.68 [0.67 to 0.69]. Conclusion: Genetic risk, age at first CAD event, and HDL cholesterol contributed the most to CAD recurrence. These features may identify high risk subgroups for treatment intensification or trials for new therapeutic strategies among those with CAD.
Abstract P558: Association of Reproductive Characteristics With Cardiometabolic Risk Factors in Women in India an Analysis of Nationally Representative Data
Authors: Vinita Subramanya, Shivani A Patel, Jithin Sam Varghese, Shakira F Suglia, K M Narayan, Alvaro Alonso
Journal: Circulation (2023)

Introduction: In addition to established risk factors for cardiovascular disease, women have unique biological characteristics related to reproduction that may further contribute to their CV risk. Among South Asian Indians, this aspect has been understudied. This study addresses this gap by evaluating the relationship between reproductive characteristics and cardiometabolic risk factors (CMRF) among women in India. Methods: We analyzed data from a community-based nationally representative sample of women aged 15-49 in the National Family Health Survey-5 (N= 724,115). Primary exposures (self-reported) included age at union and first delivery, use of contraception and history of pregnancy loss. Study outcomes (self-reported, objectively measured) were prevalent hypertension (HTN), diabetes mellitus (DM) and obesity. We estimated the association between each exposure and outcome using survey-weighted multivariable Poisson regression models adjusted for age, religion, caste, location, education and employment. Results: Prevalence (95% CI) of HTN (measured blood pressure of &gt;=140/90 mm Hg), DM (self-reported or on medications to lower blood glucose levels) and obesity (body mass index &gt; 25kg/m 2 ) was 25.8 (25.5, 26.2)%, 1.9 (1.8, 1.9)% and 24 (23.8, 24.2)%, respectively. Younger age at union and first delivery and, use of contraception [PR (95% CI): 1.13 (1.11, 1.16)] were associated with higher obesity. Pregnancy loss (due to miscarriage or abortion) was associated with higher prevalent DM [PR (95% CI): 1.21 (1.03, 1.41)] and obesity [PR (95% CI): 1.26 (1.22, 1.31)] ( Table ). Conclusion: Reproductive characteristics (age at union and first delivery, and pregnancy loss) are linked to higher prevalence of CMRF. These results provide impetus for screening for reproductive history and its inclusion in risk prediction algorithms for cardiovascular risk among Indian women. Table: Cross-sectional associations between reproductive characteristics with cardiometabolic risk factors, in the NFHS-5 (N= 724,115)
Abstract P393: AHA Life’s Essential 8 and Incident Hypertension Among US Hispanics/Latinos: Results From the Hispanic Community Health Study/Study of Latinos
Authors: Julien Tremblay, Natalie A Bello, Robert A Mesa, Neil Schneiderman, Tatjana Rundek, Fernando Testai, Amber Pirzada, Martha L Daviglus, Krista Perreira, Linda Gallo, Frank Penedo, Daniela Sotres-Alvarez, Sylvia Wassertheil-Smoller, Tali Elfassy
Journal: Circulation (2023)

Background: The American Heart Association’s Life Essential 8 (LE8) are a set of eight simple health metrics used to define cardiovascular (CV) health and promote healthy behaviors. Our objectives are to: 1) describe for the first time, LE8 among Hispanics/Latinos of diverse backgrounds and 2) determine the association between LE8 and incident hypertension, a leading risk factor for CV disease. Methods: The Hispanic Community Health Study/Study of Latinos is a population-based study of diverse Hispanics/Latinos aged 18-74 years from four US communities. Participants were examined in 2008-2011 (visit 1) and 2014-2017 (visit 2). At visit 1, information on behavioral factors (diet, smoking status, physical activity, sleep duration) and clinical factors (BMI, blood pressure, cholesterol, fasting glucose, and medication use) were measured and used to estimate a LE8 score (range: 0 to 100%) for 14,772 participants with complete information. Ideal cardiovascular health (ICH) was defined by LE8 ≥ 80%. Hypertension was defined as systolic BP ≥130 mmHg or diastolic BP ≥80 mmHg, or self-reported use of antihypertensive medications. We estimated ICH and described LE8 score according to Hispanic/Latino background group. Among the 5,667 participants free from hypertension at visit 1, we used Poisson regression models to determine the association between LE8 and incident hypertension at visit 2 including time between visits as an offset. Models were adjusted for age, sex, Hispanic/Latino background, income, education, nativity, health insurance, and marital status. All analyses accounted for the complex survey design of the study. Results: Among diverse US Hispanics/Latinos with a mean age of 41, 21.6% (SE: 0.7) had ICH. Mean LE8 score (68.2, SE: 0.3) varied by Hispanic/Latino background (p&lt;0.05). Compared with Mexican background, (mean: 72.6, SE: 0.3), LE8 was significantly lower (less favorable) in all other Hispanic/Latino background groups: mean score of 62.2 (SE: 0.4) among Puerto Ricans; 62.3 (SE: 0.5) among Cubans; 69.3 (SE: 0.4) among Central Americans, 70.2 (SE: 0.5) among Dominicans; and 70.2 (SE: 0.7) among South Americans. Among Hispanics/Latinos without hypertension at Visit 1, each 10% decrement in LE8 score was associated with 23% increased risk of hypertension over approximately six years (incident density ratio: 1.23, 95% CI: 1.16, 1.30). Conclusion: Only one in five Hispanics/Latinos had ICH and LE8 varied substantially across Hispanic/Latino background group. Improvements in other components of CV health may result in lower risk of developing hypertension.